Integrated top-down and bottom-up proteomics mass spectrometry for the characterization of endogenous ribosomal protein heterogeneity

Ribosomes are abundant,large RNA-protein complexes that are the sites of all protein synthesis in cells.Defects in ribosomal proteins(RPs),including proteoforms arising from genetic variations,alternative splicing of RNA transcripts,post-translational modifications and alterations of protein expression level,have been linked to a diverse range of diseases,including cancer and aging.Comprehensive characterization of ribosomal proteoforms is challenging but important for the discovery of potential disease biomarkers or protein targets.In the present work,using E.coli 70S RPs as an example,we first developed a top-down proteomics approach on a Waters Synapt G2 Si mass spectrometry(MS)system,and then applied it to the HeLa 80S ribosome.The results were complemented by a bottom-up approach.In total,50 out of 55 RPs were identified using the top-down approach.Among these,more than 30 RPs were found to have their N-terminal methionine removed.Additional modifications such as methylation,acetylation,and hydroxylation were also observed,and the modification sites were identified by bottomup MS.In a HeLa 80S ribosomal sample,we identified 98 ribosomal proteoforms,among which multiple truncated 80S ribosomal proteoforms were observed,the type of information which is often overlooked by bottom-up experiments.Although their relevance to diseases is not yet known,the integration of topdown and bottom-up proteomics approaches paves the way for the discovery of proteoform-specific disease biomarkers or targets.

多维液相色谱 bottom-up top-down 阵列式 完整蛋白质 蛋白质分离

蛋白质组学出现之后,多维高效液相色谱（multidimensional HPLC,MD-HPLC）系统以其快速、高效、自动化程度高以及容易与质谱等其他技术联用等优势而成为蛋白质组学相关分析技术中研究应用的热点。本文主要以本实验室在蛋白质组学研究中的技术进展为主线,介绍了多维高效液相色谱技术的发展,包括经典的“bottom-up”技术和“top-down”式的多维高效液相色谱技术路线,以及为了提高系统的分离通量而自行设计搭建的阵列式多维高效液相色谱平台,这些技术路线在蛋白质组学研究中有着极大的潜在应用价值。

Bottom-Up和Top-Down结合的网络资源规划系统结构研究

为了降低CAPEX和OPEX,运营商需要运营恰到好处的网络规模和Service Ready的服务开通。本文提出了Bottom-Up和Top-Down结合的网络资源规划系统结构,其能够预测未来资源利用率过高或过低及容量不足的网络资源,有利于运营商进行准确的网络资源扩容,从而提升网络建设ROI;能够自动化地实现从业务和市场规划到最终的网络资源规划的转换,从而提高网络资源规划的准确性和效率。

A new model for China’s CO_(2) emission pathway using the top-down and bottom-up approaches

Detailed research on China's CO_(2) emission pathway of the 2030 peak and 2060 carbon neutrality goals is fundamental to promote China's climate change action.Previous studies on emission pathways have been based on long-term emission data or model analyses.However,few studies have achieved synergy and pathway optimization at both the micro and macro levels or focused on China's 2060 carbon neutrality goal,making it difficult to support the systematic management of national and regional emission pathways.In this study,we developed an integrated CO_(2) emission pathway model,the Chinese Academy of Environmental Planning Carbon Pathways 1.2 model,under China's climate change goals.Our pathway coupled the top-down and bottom-up approaches and conducted optimization analysis under social fairness and optimal cost conditions.The results provide a clear CO_(2) emission pathway and offer insights for implementing fine management of CO_(2) emissions at the national,regional,sectoral,and spatial gridded levels.

人工智能研究中的Bottom-up方法和Top-down方法

将人工智能研究在方法上区分为Bottom-up派和Top-down派,并且分别叙述了这两种方法的哲学、历史和成果。主张两种方法走向极端是不可取的,人工智能研究要寻找两种方法的结合点,才可能避免任何一种极端方法所导致的研究复杂性。

top-down法与bottom-up法评定黑臭水体氧化还原电位测量不确定度的比较研究

分别对top-down法与bottom-up法(GUM法)中控制图法评定黑臭水体中氧化还原电位测量不确定度的评定过程及结果进行比较,两种方法评定出来的氧化还原电位不确定度基本一致,提出在质控数据符合正态分布的前提下,从控制图法引入移动极差作为中间量进行叠加检验,可更直观的体现出时间参数对质控数据的测量不确定度的影响。

语法教学中“Top-down”和“Bottom-up”方法的整合——名词性从句教学实例

针对高中英语语法教学中常出现的"只见树木不见森林"的现象,本文结合名词性从句教学课堂实例,探索了在语法教学中整合"Top-down(自上而下)"与"Bottom-up(自下而上)"的方法。四节课的设计遵循高频复现原理,侧重复合句结构,一节课强调一个连接词,配合形式多样的教学手段辅助学生形成复合句的整体概念。无论是操练的正确率还是以诗歌为主体的产出成果均验证了整合两种教学方法的有效性,但同时也反映出部分学生在基本概念上的缺失,为接下来的教学活动的调整提供了参考。

“Top-down” and “Bottom-up” approaches to teaching listening,when and which approach may be more useful?

This paper mainly deals with two mainstreams in teaching listening comprehension:bottom-up processing approach and top-down processing approach.In the first part of the essay the importance of listening comprehension in language learning will be demonstrated briefly.Then the author will go on to explore the nature of top-down and bottom-up approaches in teaching listening.Lastly,at the third part of the essay,the author shall try to discuss the possibility of applying these approaches into practice,that is,when and why one of them is more useful.Furthermore in this section,a more integrated view will be introduced.

The Effectiveness of Top-Down and Bottom-Up Process in Listening Comprehension

Top-down and bottom-up processes are two popularly-used method in teaching listening,but each of them has deficiencies.This essay will attempt to demonstrate that both top-down process and bottom-up process are necessarily useful,and adopting them appropriately conduce to effective and efficient listening comprehension.The first section of this paper will critically examine the advantages and disadvantages of the two processes.It will then illustrate the benefit of employing them in an interactive way.

Study on reading strategies in college English teaching： Top-down or bottom-up？

Reading comprehension ability is one of the key abilities trained in College English teaching in China. This paper first examines the theories behind top-down and bottom-up reading strategies, and then suggests top-down reading strategies are more effective than the bottom-up ones in training EFL learners to be efficient readers in English. In particular, taking into account the English proficiency and the cognitive ability of the Chinese university students （non-English major）, the author argues that more priorities should be given to the top-down reading strategies training in EFL reading class.

英语听力教学“Top-down”和“Bottom-up”使用策略分析

“Top-down”和“Bottom-up”是在英语听力教学中两种重要的策略。“Top-down”是听者根据上下语境去猜测听到的大致内容;“Bottom-up”指的是从单个的词汇开始逐个记录,直到获取整个句子的含义。总体上来说,“Top-down”听力策略更适用于英语水平较高的学习者,因为他们已经能比较轻松地识别大部分的常用词汇;而“Bottom-up”听力策略则对英语水平较低的学习者有很大帮助,可以为他们打下坚实的听力基础。但“Top-down”和“Bottom-up”都有其局限性。教师应该在实际的听力教学中保持这两种听力策略练习的平衡性,教会学生如何根据自身的英语水平、不同的学习目标及语境差异灵活地将这两种策略结合起来。

Historical Evolution of the Trophic and Limnological Relationships in the Itaipu Reservoir:Top-Down and Bottom-Up Effects upon Fish Production

Many experimental studies have contributed to the development of the theory of trophic chains in lacustrine habitats. They have revealed the important role played by fish, a subject that has been mostly ignored by limnological studies for the past few decades. Most of these studies were developed in Europe and in the United States. The general applicability of this theory has not yet been tested in subtropical and tropical habitats. In spite of controversies, the bottom-up: top-down trophic cascade hypotheses are the most adopted conceptual models. In this context, we examined if these hypotheses may be corroborated by data from the subtropical Itaipu Reservoir. A negative effect was verified between water transparency and total suspended solids. The detritivorous fish exerted a controlling effect on chlorophyll-a concentrations. Bottom-up effects were detected in four trophic levels, and top-down was detected in just one trophic level. The limnological variates influenced the chlorophyll-a concentration, which indicated that the lnTKN plus the effect of the quarter and the reservoir zone (and their interaction) were important.

Novel fabrication techniques for ultra-thin silicon based flexible electronics

Flexible electronics offer a multitude of advantages,such as flexibility,lightweight property,portability,and high durability.These unique properties allow for seamless applications to curved and soft surfaces,leading to extensive utilization across a wide range of fields in consumer electronics.These applications,for example,span integrated circuits,solar cells,batteries,wearable devices,bio-implants,soft robotics,and biomimetic applications.Recently,flexible electronic devices have been developed using a variety of materials such as organic,carbon-based,and inorganic semiconducting materials.Silicon(Si)owing to its mature fabrication process,excellent electrical,optical,thermal properties,and cost efficiency,remains a compelling material choice for flexible electronics.Consequently,the research on ultra-thin Si in the context of flexible electronics is studied rigorously nowadays.The thinning of Si is crucially important for flexible electronics as it reduces its bending stiffness and the resultant bending strain,thereby enhancing flexibility while preserving its exceptional properties.This review provides a comprehensive overview of the recent efforts in the fabrication techniques for forming ultra-thin Si using top-down and bottom-up approaches and explores their utilization in flexible electronics and their applications.

Top-down知觉加工下的视觉传导特征

目的:研究Top-down知觉通路参与儿童视觉传导效率及其特征。方法:选取2020-01/06于我院门诊进行健康查体的儿童志愿者26名,采用儿童自我颜面部特征明显的照片作为Top-down知觉注视点图片,通过图形视觉诱发电位(PVEP)检查记录N75潜时、P100波峰时间、P100波幅及P100复极化时间。结果:不同视知觉加工路径对N75潜时无显著影响,而不同空间频率对N75潜时具有显著影响,高频空间刺激下N75潜时延长。视知觉加工路径与空间频率的交互作用对P100峰值时间呈现显著影响,Top-down条件下,高频空间刺激时P100波峰值出现时间显著缩短。不同视知觉加工路径和空间频率均对P100波幅影响显著,高频空间刺激下,Top-down知觉途径对P100波幅的影响显著。不同视知觉加工路径和空间频率均对P100波复极化时间影响显著,而加工路径与空间频率的交互作用影响不显著。结论:Top-down知觉途径参与下的儿童视觉过程视觉传导速度得到提高,视觉传导效率提高。

The Application of The Top-down Approach in Teaching Extensive Reading

The top-down and bottom-up are two main approaches used in teaching extensive reading and both of them should be used alternatively so that students can not only understand the details but also the main ideas of reading materials.The importance of using top-down approach is emphasized and some suggestions are given on the problem that students pay so much attention on vocabulary and grammar rather than main idea in reading.

Pro/Engineer Top-down Design在复点机系列产品开发中的应用

论述了Pro/Engineer Top-down Design设计理念及Top-down Design的优点、原则、所用到的工具和设计过程。以复点机的设计开发过程为例,详尽论述了Top-down Design的具体实施过程,为应用Top-down Design在产品设计开发的具体实施,提供理论依据和过程指导。

Top-down control on major groups of global marine diazotrophs

Dinitrogen(N_(2))fixed by a group of prokaryotes(diazotrophs)is the dominant process adding bioavailable nitrogen into the ocean.Although it has been intensively studied how N_(2) fixation is controlled by resources(bottom-up factors),it is unclear whether the grazing(top-down control)effectively impacts growth and distribution of different diazotroph groups.In this study,we evaluate this question by conducting log-log regression of diazotroph biomass onto corresponding N_(2) fixation rates in the global ocean.The slope of the regression for Trichodesmium is~0.8,indicating that a small portion of the increase in N_(2) fixation does not accumulate as its biomass.This leads to a conclusion that Trichodesmium is under a substantial top-down control,although bottom-up control still dominates.We also analyze the residuals of the regression in the North Atlantic,concluding that free trichomes of Trichodesmium are subject to stronger top-down control than its colonies.The weak correlation between the biomass and N_(2) fixation of unicellular cyanobacterial diazotrophs indicates that the degree of top-down control on this type of diazotrophs varies greatly.The analyses obtain unrealistic results for diatom-diazotroph assemblages due to complicated nitrogen sources of these symbioses.Our study reveals the variability of top-down control among different diazotroph groups across time and space,suggesting its importance in improving our understandings of ecology of diazotrophs and predictions of N_(2) fixation in biogeochemical models.Measurements of size-specific N_(2) fixation rates and growth rates of different diazotroph groups can be useful to more reliably analyze the top-down control on these key organisms in the global ocean.

水生所浮游动物下行效应控藻机制的研究获进展

中国科学院水生生物研究所关于浮游动物下行控藻机制的研究论文＂Increasing zooplankton size diversity enhances the strength of top-down control on phytoplankton through diet niche partitioning＂在动物和生态学领域重要期刊《Journal of Animal Ecology》在线发表。首次报道了浮游动物个体大小多样性影响下行控藻效应的一种新机制。

自上而下和自下而上相结合提高大规模生态修复规划的实用性和效率——来自社会生态系统的启示

Ecological restoration policies and their implementation are influenced by ecological and socioeconomic drivers.Top-down approach-based spatial planning,emphasizing hierarchical control within government structures,and without a comprehensive consideration of social–ecological interactions may result in implementation failure and low efficiency.Although many researchers have indicated the necessity to engage social–ecological interactions between stakeholders in effective planning processes,socioeconomic drivers of ecological restoration on a large scale are difficult to quantify because of data scarcity and knowledge limitations.Here,we established a new ecological restoration planning approach linking a social–ecological system framework to large-scale ecological restoration planning.The new spatial planning approach integrates bottom-up approaches targeting stakeholder interests and provides social considerations for stakeholder behavior analysis.Based on this approach,a meta-analysis is introduced to recognize key socioeconomic and social–ecological factors influencing large-scale ecological restoration implementation,and a stochastic model is constructed to analyze the impact of socioeconomic drivers on the behavior of authorities and participants on a large scale.We used the Yangtze River Basin-based Conversion of Cropland to Forest Program(CCFP),one of the largest payments for ecosystem service programs worldwide,to quantify the socioeconomic impacts of large-scale ecological restoration programs.Current CCFP planning without socioeconomic considerations failed to achieve large-scale program goals and showed low investment efficiency,with 19.71% of the implemented area reconverting to cropland after contract expiry.In contrast,spatial matching between planned and actual restoration increased from 61.55% to 81.86% when socioeconomic drivers were included.In addition,compared to that with the current CCFP implementation,the cost effectiveness of spatial planning with social considerations improved by 46.94%.Thus,spatial optimization planning that integrates both top-down and bottom-up approaches can result in more practical and effective ecological restoration than top-down approaches alone.Our new approach incorporates socioeconomic factors into large-scale ecological restoration planning with high practicality and efficiency.

p‑Type Two‑Dimensional Semiconductors:From Materials Preparation to Electronic Applications

Two-dimensional(2D)materials are regarded as promising candidates in many applications,including electronics and optoelectronics,because of their superior properties,including atomic-level thickness,tunable bandgaps,large specific surface area,and high carrier mobility.In order to bring 2D materials from the laboratory to industrialized applications,materials preparation is the first prerequisite.Compared to the n-type analogs,the family of p-type 2D semiconductors is relatively small,which limits the broad integration of 2D semiconductors in practical applications such as complementary logic circuits.So far,many efforts have been made in the preparation of p-type 2D semiconductors.In this review,we overview recent progresses achieved in the preparation of p-type 2D semiconductors and highlight some promising methods to realize their controllable preparation by following both the top-down and bottom-up strategies.Then,we summarize some significant application of p-type 2D semiconductors in electronic and optoelectronic devices and their superiorities.In end,we conclude the challenges existed in this field and propose the potential opportunities in aspects from the discovery of novel p-type 2D semiconductors,their controlled mass preparation,compatible engineering with silicon production line,high-κdielectric materials,to integration and applications of p-type 2D semiconductors and their heterostructures in electronic and optoelectronic devices.Overall,we believe that this review will guide the design of preparation systems to fulfill the controllable growth of p-type 2D semiconductors with high quality and thus lay the foundations for their potential application in electronics and optoelectronics.